Bioinformatics analysis of miRNA and its associated genes to identify potential biomarkers of oral submucous fibrosis and oral malignancy

Abstract

Background: MicroRNAs are a group of non-coding RNA that controls the gene expression. The interaction between miRNA and mRNA is thought to be dynamic. Oral cancer “The cancer of mouth” is quite prevailing in developing countries. miRNA has been found associated with oral cancer targeting tumor growth, cell proliferation, metastasis, invasion. The significant association of miRNA with genes could be used as a remarkable tool for diagnosis as well as prognostic analysis of oral cancer. Aim: The aim of the present study is to evaluate common upregulated and downregulated miRNAs in oral submucous fibrosis (OSMF) and oral malignancy (OM) patients that can be used as diagnostic biomarkers, and to find out their interactions with target genes to establish associated networks in cancer pathways. Methods and Results: Using miRDeep2 and DESeq analysis, the upregulated and downregulated miRNA in OSMF (Oral Submucous Fibrosis) and OM (Oral Malignancies) samples were compared to GEO (Gene Expression Omnibus) control dataset. There were 50 common downregulated miRNAs and 13 common upregulated miRNAs in OSMF and OM samples. miRNet analysis of common upregulated miRNA and common downregulated miRNA identified 1295 and 5954 genes, respectively connected with cancer pathways. From analysis of Hub genes, HRAS, STAT3, TP53, MYC, PTEN, CTNNB1, CCND1, JUN, VEGFA, KRAS were found associated with downregulated miRNA and VEGFA, TP53, MDM2, PTEN, MYC, ERBB2, CDKN1A, HSP90AA1, CCND1, AKTI were found associated with upregulated miRNA. The gene enrichment analysis of these hub genes were associated with cell communication, metabolic process, cell proliferation, and cellular component organization. Hub Genes linked with upregulated miRNA had an enrichment ratio of 11.828, whereas hub genes linked with downregulated miRNA had an enrichment ratio of 45.912. Conclusion: We identified common deregulated miRNAs between OSMF and OM patients, which were further analyzed to find out associations with the genes correlated to cancer pathways. The hub genes identified in this study were found to have a significant impact on tumor growth and carcinogenesis. Also, the enrichment of these genes has revealed that the genes are associated with cellular communication, metabolic processes and various biological regulation. These deregulated miRNAs can be used to make a panel of biomarkers to diagnose oral cancer from blood even before its onset.